CD24 Polymorphisms Research Articles

Association between Cluster of Differentiation 24 (CD24) Polymorphism, Talin-1 gene expression and Hepatocellular Carcinoma prevalence in Egyptian population

IntroductionBackground: Hepatitis C is considered as one of the most popular diseases in Egypt. Our aim is to clarify the association between Cluster of Differentiation 24 (CD24) polymorphism, Talin-1 gene expression and the prevalence of hepatocellular carcinoma in Egyptian Hepatitis C virus patients.Material and methodsThe link between CD24 polymorphism rs8734 and the prevalence of hepatocellular carcinoma was assessed between 200 control subjects and 400 hepatitis C virus patients (HCV), patients were classified as follows; 200 patients with HCV and 200 with HCV and hepatocellular carcinoma (HCC) by histopathological assessment and PCR-restriction fragment length polymorphism (PCR-RFLP).ResultsResults: The hepatitis c patients with HCC showed significant increase in alpha fetoprotein (AFP) and Talin-1 gene expression compared to patients with HCV as well as in healthy volunteers. Furthermore, the frequencies of CD 24 170 CT/TT genotype were significantly higher in HCV patients without complications (60%) when compared to CC genotype (40%) (OR= 6 at X2= 14.41, P = 0.0007), and in HCV with HCC patients (90%) when compared to CC genotype (10%) (OR= 36 at X2= 14.41, P = 0.0007).ConclusionsThese data suggests that CD24 genetic polymorphism rs8734 and Talin-1 gene expression may be a significant determinant for the prevalence of hepatocellular carcinoma in HCV patients.

Evaluation of two functional CD24 polymorphisms in primary sclerosing cholangitis

Background: Primary sclerosing cholangitis (PSC) is a progressive liver disease and characterized by chronic inflammation, sclerosis and strictures of bile ducts. Several genetic risk factors might contribute to pathogenesis. Functional single nucleotide polymorphisms (SNPs) in the CD24 gene have been associated with the development of autoimmune and autoinflammatory diseases and might contribute to the susceptibility for inflammatory bowel disease (IBD).Aim: This retrospective study aimed to evaluate the impact of two functional CD24 SNPs on clinical features and disease progression in patients with PSC.Methods: A C to T coding polymorphism (rs8734) and a TG deletion in the 3´- untranslated region (rs3838646) were genotyped. The study cohort comprises of 359 PSC patients for rs3838646 genotype and 335 PSC patients for rs8734 genotype. Clinical and laboratory parameters were collected by chart review.Results: For the rs8734 genotype, 175 patients (52.2%) were found to be homozygous wildtype (‘Ala/Ala’), 127 (37.9%) patients were heterozygous (‘Ala/Val’) and 33 patients (9.9%) were homozygous mutant (‘Val/Val’). The rs8734genotype was associated with a decreased risk for dominant strictures at first diagnosis of PSC (p = .04). For the rs3838646 genotype, 322 patients (89.7%) were found to be homozygous wildtype (‘TG/TG’); 37 showed the ‘TG/del’ genotype (10.3%). The ‘TG/del’genotype was associated with alower risk of IBD (p = .01).There was no influence of both CD24 SNPs with clinical end points or transplantation-free survival in our PSC cohort.Conclusion: Our results suggest a mild association of the rs8734 CD24 genotype with dominant strictures at first diagnosis of PSC. The rs3838646 CD24 genotype is associated with a lower rate of IBD. Both SNPs seem to modulate the clinical phenotype without major pathogenetic importance for disease progression in PSC.

Su1974 CD24 Polymorphisms Are Associated With Obesity Risk

Su1974 CD24 Polymorphisms Are Associated With Obesity Risk

CD24 and APC Genetic Polymorphisms in Pancreatic Cancers as Potential Biomarkers for Clinical Outcome.

BackgroundThere are no validated biomarkers that correlate with the prognosis of pancreatic ductal adenocarcinoma (PDA). The CD24 and adenomatous polyposis coli (APC) genes are important in the malignant transformation of gastrointestinal cells. This study examined APC and CD24 genetic polymorphisms and their possible impact on survival of patients with PDA.MethodsClinical and pathological data as well as blood samples for extracting DNA were obtained for 73 patients with PDA. Real-time PCR assessed genetic variants of APC (I1307K and E1317Q), and four different single nucleotide polymorphisms (SNPs) in the CD24 gene: C170T (rs52812045), TG1527del (rs3838646), A1626G (rs1058881) and A1056G (rs1058818).ResultsThe median age at diagnosis was 64 (41–90) years. Thirty-one patients (42.5%) were operable, 16 (22%) had locally advanced disease and 26 (35.5%) had disseminated metastatic cancer. The malignancy-related mortality rate was 84%. Median survival was 14 months (11.25–16.74). Survival was similar for wild-type (WT), heterozygous and homozygous variants of the APC or CD24 genes. The three most frequent CD24 SNP combinations were: heterozygote for A1626G and WT for the rest of the alleles (14% of patients), heterozygote for C170T, A1626G, A1056G and WT for the rest (14% of patients), and heterozygote for C170T, A1056G and WT for the rest (10% of patients). All patients were APC WT. The first two groups were significantly younger at diagnosis than the third group.ConclusionsSpecific polymorphisms in the APC and CD24 genes may play a role in pancreatic cancer development. Correlation with survival requires a larger cohort.

Contribution of CD24 polymorphisms to autoimmune disease: A meta-analysis

PurposeTo determine the relationship between two CD24 polymorphisms, rs8734/rs52812045 and rs3838646, and autoimmune disease. DesignMeta-analysis. MethodsThe Medline, EMBASE, Web of Science, and Cochrane Library databases were searched for studies reporting the association between CD24 polymorphisms and autoimmune disease. Two of the authors selected eligible studies and extracted and analyzed the data independently. ResultsCompared with carriers of the C allele (CC, CT, CT+CC), individuals homozygous for the T allele (TT) and heterozygous (CT+TT) at rs8734/rs52812045 have a higher incidence of autoimmune disease, whereas rs3838646 is not associated with autoimmune disease. Subgroup analysis found an increased risk of multiple sclerosis with the TT vs. CC, TT vs. CT, and TT vs. CC+CT alleles. ConclusionThe CD24 polymorphism rs8734/rs52812045 contributes to the development of autoimmune disease.

Associations between CD24 gene polymorphisms and inflammatory bowel disease: A meta-analysis.

To evaluate the relationships between CD24 gene polymorphisms and the risk of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). The PubMed, Web of Science and Cochrane Library databases were searched (up to May 30, 2014). The search terms "CD24", "inflammatory bowel disease", "Crohn's disease", "Ulcerative colitis", "IBD", "CD" or "UC"; and "polymorphism", "mutation" or "variant" were used. Association studies were limited to the English language, but no limitations in terms of race, ethnicity or geographic area were employed. Stata SE12 software was used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered statistically significant. The information was independently extracted from each eligible study by two investigators. Two common polymorphisms, C170T (rs8734) and TG1527del (rs3838646), in the CD24 gene were assessed. A total of three case-control studies including 2342 IBD patients and 1965 healthy controls were involved in this meta-analysis. The patients and controls were from Caucasian cohorts. The three articles included in this meta-analysis all conformed to Hardy-Weinberg equilibrium. This meta-analysis revealed that there were no significant associations between the two CD24 polymorphisms and the risk for IBD (all P > 0.05). However, in a disease subgroup analysis, we found that the CD24 C170T polymorphism was associated with an increased risk of UC in a dominant model (OR = 1.79, 95%CI: 1.15-2.77, P = 0.009) and an additive model (OR = 1.87, 95%CI: 1.19-2.93, P = 0.007), but this relationship was not present for CD. The CD24 TG1570del polymorphism was significantly associated with CD in the additive model (OR = 1.24, 95%CI: 1.01-1.52, P = 0.037). Our findings provide evidence that the CD24 C170T polymorphism might contribute to the susceptibility to UC, and the CD24 TG1527del polymorphism might be associated with the risk of CD.

Mo1318 CD24 Polymorphisms Are Associated With Obesity Risk

Mo1318 CD24 Polymorphisms Are Associated With Obesity Risk

Sa1244 CD24 Polymorphisms: Potential Contribution to IBD Risk and Genetic Susceptibility

Sa1244 CD24 Polymorphisms: Potential Contribution to IBD Risk and Genetic Susceptibility

Abstract 3645: CD24 polymorphisms and susceptibility to inflammatory bowel disease and colorectal cancer risk

Abstract Background: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory disorders of the gastrointestinal tract probably resulting from an aberrant immune response to luminal microbial antigens in a genetically predisposed host. Despite significant progress in the understanding and treatment of IBD, patients have an increased risk of colorectal cancer. We have previously shown that CD24 plays an important role in the multistep process of colorectal carcinogenesis and that it may be a target for chemoprevention and antitumor therapy (Sagiv, Gastroenterol, 2006; Sagiv, Can Res, 2008; Shapira, Gastroenterol 2011). However, the role of CD24 in mediating colitis has not been elucidated. Recently, single nucleotide polymorphisms (SNPs) in the CD24 gene have been associated with disease risk and progression in autoimmune diseases and may impact breast cancer prognosis. Aim: Evaluate whether CD24 SNPs are associated with a risk for IBD. Methods: The CD24 polymorphisms: C170T (rs8734), TG1527del (rs3838646), A1626G (rs1058881) and A1056G (rs1058818) were assessed in a case-control study of an Israeli cohort comprising 138 IBD patients and 105 age- and gender-matched healthy controls. Restriction fragment length polymorphism (RFLP) analysis was performed using BstX1, Bsr1, Mfe1, and BstU1 restriction enzymes, respectively. Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models. Results: C170T carriers had more IBD (OR=3.022, 95% CI: 1.748-5.223, p=0.001): UC (OR=3.002, 95% CI: 1.661-5.427, p=0.001) and CD (OR=3.077, 95% CI: 1.334-7.095 p=0.008). Carrying the A1626G and A1056G SNPs was a risk factor for IBD: OR=2.460, 95% CI: 1.420-4.259, p=0.001 and OR=1.856, 95%: 1.011-3.405, p=0.01, respectively, specifically UC: OR=2.218, 95% CI: 1.207-4.075, p=0.01 and OR=1.944, 95% CI: 0.995-3.798, p=0.01, respectively, but not for CD (p=0.086, p=0.299). A1626G and TG1527del were associated with a younger age of IBD onset (p=0.022, p=0.027, respectively). Conclusions: 1. The CD24 C170T polymorphism is associated with IBD risk. 2. CD24 A1626G and A1056G SNPs might be specifically associated with UC risk. 3. CD24 SNPs associated with an earlier onset of IBD (A1626G and TG1527del) may have a protective role. 4. CD24 may be a new IBD genetic susceptibility factor, with clinical implications in the prediction of IBD phenotype, the course of the disease, and colitis-associated cancer. Citation Format: Victoria Lisiansky, Sarah R. Kraus, Inna Naumov, Dina Kazanov, Ilana Nabiochtchikov, Ohad Toledano, Moshe Leshno, Doran Avivi, Menachem Moshkowitz, Iris Dotan, Nadir Arber. CD24 polymorphisms and susceptibility to inflammatory bowel disease and colorectal cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3645. doi:10.1158/1538-7445.AM2014-3645

Tu1940 CD24 Polymorphisms and Susceptibility to Inflammatory Bowel Disease

Tu1940 CD24 Polymorphisms and Susceptibility to Inflammatory Bowel Disease

CD24 Ala57Val polymorphism is associated with spontaneous viral clearance in the HCV-infected Chinese population.

Host immune response to hepatitis C virus (HCV) is a vital factor involved in both viral clearance and liver disease pathogenesis. CD24 plays an important role in inflammation and immune response and CD24 polymorphisms are associated with risk and progression of chronic hepatitis B virus infection. Our study evaluated whether CD24 polymorphisms affect HCV clearance. We genotyped 544 chronic hepatitis C (CHC) patients, 78 spontaneous hepatitis C clearance (SHC) patients and 215 healthy controls for CD24 gene variants at positions -P534, P170, P1527 and IFNL3 rs12979860 by pyrosequencing. In CHC patients, 362 individuals were treated with a recombinant IFN-α2b/ribavirin combination for 48weeks and were followed up for an additional 24weeks. Lymphocyte CD24 expression was analysed by flow cytometry. We show that P170 CT and CT/TT genotypes were over-represented in the SHC group compared to CHC patients (62.8% vs. 47.2% and 75.6% vs. 60.3%, for respective polymorphisms). In multivariate logistic analysis, P170 (CD24 Ala57Val) polymorphism was an independent predictor of SHC (adjusted OR=2.11, 95%CI=1.19-3.73, P=0.010 for CT genotype; OR=2.01, 95%CI=1.15-3.49, P=0.014 for CT/TT genotype). No significant associations were found between the CD24 polymorphisms and treatment-induced viral clearance in log-rank analysis and Cox regression analysis. Patients with the CT/TT genotype had greater T-cell CD24 expression than patients with the CC genotype. Our findings suggest that CD24 Ala57Val polymorphism and associated variations in CD24 expression may be an important predictor for SHC, but have no effect on antiviral drug treatment response in Chinese CHC patients.

CD24 Gene Polymorphism - A Novel Prognostic Factor in Esophageal Cancer

The CD24 gene has been correlated with poor prognosis of various malignancies. The significance of CD24 in esophageal cancer remains unknown. Our aim was to evaluate the association between CD24 genetic polymorphism and esophageal cancer. Between June 2011 and May 2012 patients with esophageal cancer and healthy controls were prospectively enrolled and clinicopathological data were collected. Genomic DNA was extracted and restriction fragment length polymorphism (RFLP) analysis was performed to determine CD24 polymorphism at the coding region of CD24, which results in a substitution of the amino acid Ala by Val. Statistical significance was determined by unpaired t-test, χ²-test, and Fisher's exact test. A total of 102 patients were included, of whom 51 had esophageal cancer and the rest comprised a healthy control group. The incidence of the polymorphism variant (Val/Val) among the healthy subjects and the esophageal cancer cohort was 6% in both groups. The incidence of N3 (metastasis in 7 or more regional lymph nodes) was markedly higher in those esophageal cancer patients who carried the polymorphism variant compared with those who did not carry it (66% and 2%, respectively, p=0.007). No significant difference was found between the groups with regard to age, gender, histology type, tumor location, tumor stage, and other histological characteristics of the tumor. This CD24 polymorphism may serve as a novel prognostic marker identifying esophageal cancer patients with poor prognosis. Further studies are warranted to evaluate CD24 function and to validate its predictive potential with regard to esophageal cancer.

Role of CD24 Polymorphisms in the Susceptibility to Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) results from an inappropriate inflammatory response in which genetic, immune, and environmental factors all play important roles. Recently, single nucleotide polymorphisms (SNPs) in the CD24 gene have been associated with the development of several autoimmune diseases. To evaluate whether CD24 SNPs, are associated with risk of ulcerative colitis (UC) and Crohn's disease (CD). The CD24 polymorphisms C170T (rs8734), TG1527del (rs3838646), A1626G (rs1058881), and A1056G (rs1058818) were assessed in a case-control study of an Israeli cohort comprising 117 IBD patients and 105 age and gender-matched healthy controls. Restriction fragment length polymorphism (RFLP) analysis was performed using BstX1, Bsr1, Mfe1, and BstU1 restriction enzymes. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression models. Carriers of the C170T SNP were at increased risk of IBD (OR=3.022, 95% CI: 1.748-5.223, p=0.001), UC (OR=3.002, 95% CI: 1.661-5.427, p=0.001) and CD (OR=3.077, 95% CI: 1.334-7.095, p=0.008). Carrying the A1626G and A1056G SNPs was found to be a risk factor for IBD (OR=2.460, 95% CI: 1.420-4.259, p=0.001 and OR=1.856, 95% CI: 1.011-3.405, p=0.01), UC (OR=2.218, 95% CI: 1.207-4.075, p=0.01 and OR=1.944, 95% CI: 0.995-3.798, p=0.01) but not for CD (p=0.086 and p=0.299). The A1626G and TG1527del were found to be associated with younger age of IBD onset (p=0.022 and p=0.027, respectively). The CD24 C170T polymorphism is associated with IBD risk. The A1626G and A1056G SNPs might be associated only with UC risk. These findings suggest CD24 as a new genetic susceptibility factor, with clinical implications in the prediction of IBD prognosis and therapy.

CD24 Polymorphisms Cannot Predict Pathologic Complete Response to Anthracycline- and Taxane-Based Neoadjuvant Chemotherapy in Breast Cancer

IntroductionTo evaluate the correlations between CD24 polymorphisms and clinicopathologic variables of patients with breast cancer. Patients and MethodsSingle-nucleotide polymorphisms (SNPs) of CD24 were genotyped by the Sequenom MassArray iPLEX Gold System in 170 patients with breast cancer, and a total of 120 patients with histologically confirmed T2-4N0-2 M0 breast cancer were recruited to therapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) as neoadjuvant chemotherapy. Data were analyzed by the chi-square test and logistic regression analysis. ResultsThere were no significant correlations between CD24 polymorphisms and any of the clinicopathologic variables, and no significant associations were found between either of the polymorphisms and CD24 protein expression. The clinical response rate and the pathologic complete response (pCR) rate were 68.8% and 27.1% in patients with the CD24 rs3838646 CA/CA genotype, and 87.5% and 20.8% in CD24 CA/Del and Del/Del genotype. There were no statistically significant differences between the CA/CA group and the Del allele group. The clinical response rate was 85.4% in patients with the CD24 rs52812045 C/C genotype and 63.9% in patients with the CD24 C/T and T/T genotype. There was a statistically significant difference between the C/C group and the T allele group (odds ratio = 0.28; 95% confidence interval, 0.11-0.73, P = .01). The pCR rate was 29.2% in patients with the CD24 rs52812045 C/C genotype and 23.6% in patients with the CD24 C/T and T/T genotype. There were no statistically significant differences between the C/C group and the T allele group. In a multivariate analysis, there was no correlation between CD24 rs3838646 or rs52812045 genotype and pCR. ConclusionCD24 rs3838646 and rs52812045 polymorphism could not predict the pathologic complete response to anthracycline- and taxane-based neoadjuvant chemotherapy in breast cancer. Additional larger studies are required to confirm this finding.

Association between CD24 polymorphism and genetic susceptibility to breast cancer: a case-control study

To evaluate the association between CD24 polymorphism and genetic susceptibility to breast cancer in Chongqing women of Han nationality. In the case-control study, single nucleotide polymorphism of CD24 (rs3838646 and rs52812045) was genotyped by Sequenom MassArray®iPLEX GOLD System in 170 patients with breast cancer and 178 healthy controls. Data were analyzed via t test, Chi-square test, and logistic regression analysis. The distribution of CD24 rs3838646 genotype and allelotype had no significant difference between the patients with breast cancer and healthy controls (χ2=3.54, P=0.17; χ2=2.29, P=0.13). Stratified by menstruation status, premenopausal individuals carrying CD24 rs3838646 Del allele significantly reduced the risk (OR=0.51, 95% CI 0.26-1.00, P=0.0485) of breast cancer compared with the individuals carrying CD24 CA/CA genotype. The distribution of CD24 rs52812045 genotypes and allelotypes had no significant difference between the patients with breast cancer and healthy controls (χ2=5.37, P=0.07; χ2=3.05, P=0.08). Compared with C/C homozygotes, CD24 rs52812045 T/T homozygotes had a significantly reduced risk (OR=0.47, 95% CI 0.23-0.95; P=0.04) for breast cancer. CD24 polymorphism may be a marker for susceptibility to breast cancer in Han population in southwestern China. CD24 polymorphisms may be associated with a reduced risk of breast cancer in Chinese population. Further studies are needed to confirm these findings.

Tu1902 A CD24 Polymorphism Is Associated With Early Onset and High Rate of Recurrence Among Colorectal Cancer (CRC) Patients

Tu1902 A CD24 Polymorphism Is Associated With Early Onset and High Rate of Recurrence Among Colorectal Cancer (CRC) Patients

CD24 polymorphisms in breast cancer: impact on prognosis and risk

Overexpression of CD24 has a negative impact on breast cancer prognosis. We have recently reported that the CD24 codon 57 Val/Val genotype (rs52812045) is associated with pathologic complete response after neoadjuvant chemotherapy for primary breast cancer and correlates with intratumoral lymphocyte infiltrates. This study was performed to investigate the influence of CD24 polymorphisms on breast cancer prognosis and risk. A total of 2,514 patients and 4,858 controls recruited as part of the MARIE study, a population-based case-control study, were genotyped for two CD24 polymorphisms (rs52812045, rs3838646) using TaqMan custom genotyping assays. Associations with overall and breast cancer-specific survival were assessed using uni- and multivariable Cox regression models stratified by age at diagnosis and adjusted for prognostic factors. Conditional logistic regression analysis adjusted for major risk factors was used to estimate multivariable odds ratios for risk of putative allele carriers compared to wildtype carriers. CD24 Ala/Val was significantly associated with breast cancer prognosis [Val/Val hazard ratio (HR)(adjusted)=1.52; 95% confidence interval (CI): 1.00-2.30, p=0.05 and HR(adjusted)=1.83; 95% CI: 1.10-3.05, p=0.018 for all-cause and breast cancer-specific mortality, respectively). The association was significant only in patients with a BMI<25 and in those who received adjuvant chemotherapy. None of the CD24 alleles was associated with breast cancer risk. These results provide further evidence of the CD24 Val/Val genotype influencing outcome in primary breast cancer. Together with previous data of CD24 overexpression as a poor prognostic marker, the findings underline the biological importance of CD24 for breast cancer.

CD24 Ala57Val polymorphism predicts pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer

Overexpression of CD24 is an independent prognostic factor for breast cancer. Recently, two polymorphisms in the CD24 gene were linked to disease risk and progression in autoimmune diseases. Here, we evaluated the clinical relevance of these polymorphisms with respect to their potential to predict a pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC), one of the strongest prognostic factors in this setting. A total of 257 patients were randomized to either doxorubicin/cyclophosphamide (AC) or doxorubicin/pemetrexed (AP), both followed by docetaxel (Doc) as NCT for T2-4 N0-2 M0 PBC as part of an international, multicenter, randomized phase II trial. CD24 polymorphisms were analyzed on germ line DNA and correlated with clinicopathologic variables and pCR. No significant associations were found between either of the polymorphisms and any of the clinicopathologic variables. In a multivariate analysis, CD24 Val/Val genotype was the only significant predictor of pCR (OR: 4.97; P = 0.003). The predictive potential was significant in both treatment arms and in the hormone receptor-positive subgroup. There was no correlation between CD24 3'UTR (TG/Del) genotype and pCR. We did not observe any association between CD24 genotype and CD24 protein expression or in vitro chemosensitivity, but there was a significant correlation between CD24 Val/Val and intratumoral lymphocyte aggregates. In conclusion, CD24 Ala/Val SNP is a strong and independent predictor of pCR after NCT for PBC and may affect immune functions rather than tumor characteristics. Further evaluation of the CD24 function and validation of its predictive potential are clearly warranted.

Analysis of the influence of two CD24 genetic variants in Crohn's disease and ulcerative colitis

The aim of this study was to evaluate the possible implication of CD24 gene in the genetic predisposition to inflammatory bowel disease (IBD). Our study population consisted of 1321 female Spanish individuals (369 Crohn's disease [CD] patients, 323 ulcerative colitis [UC] patients, and 629 healthy matched controls). Two putative functional polymorphisms, a C to T coding polymorphism (rs8734) and a TG deletion in the 3′ untranslated region (rs3838646), were used as CD24 genetic markers and genotyped using a Taqman 5′ allelic discrimination assay. The “del” allele of the dinucleotide deletion was associated with an increased risk of CD (odds ratio = 1.61, 95% confidence interval = 1.17–2.21, p FDR = 6.4E-03) but not with UC. Moreover, this allele was significant associated with the age of CD diagnosis between 17 and 40 years, the ileocolonic location, and the inflammatory behavior of CD. We observed no significant differences between the allelic or genotypic frequencies of the A57V polymorphism in our studied IBD cohort. Our results suggest that the rs3838646 CD24 polymorphism is part of the genetic background of CD.

Predictive value of CD24 ala/val polymorphism for pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer.

543 Background: Cytoplasmic expression of CD24, a GPI-anchored glycoprotein, is a strong prognostic factor for breast cancer and many other solid tumors. Recently, two polymorphisms in the CD24 gene (rs8734, rs3838646) have been linked to disease risk and progression in multiple sclerosis (MS), systemic lupus erythematodes (SLE) as well as the risk and progression of chronic hepatitis B infection. This study was designed to evaluate the clinical relevance of these polymorphisms in breast cancer with respect to their potential to predict a pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC), one of the strongest prognostic factors in this setting. Methods: 257 patients were randomized to either doxorubicin/cyclophosphamide (AC) or doxorubicin/pemetrexed (AP) both followed by docetaxel (Doc) as NCT for T2-4 N0-2 M0 PBC as part of an international, multicentric, randomized phase II trial. Both CD24 polymorphisms were analyzed on germline DNA and correlated with clinicopathologic variables and pCR. Results: There were no significant associations between either polymorphism and any of the clinicopathologic variables. In a multivariate analysis of both treatment arms, CD24 Val/Val genotype (rs8734) was the only significant predictor of pCR (OR: 4.97; p = 0.003). A test for interaction between CD24 Ala/Val genotype and treatment was negative (p = 0.49) and the predictive potential of this SNP was significant in both treatment arms. There was no correlation between CD24 3′UTR (TG/Del) genotype and pCR. Data on associations between genotype and CD24 expression as well as tumor associated lymphocytes will be presented. Conclusions: The CD24 Ala/Val SNP is a strong and independent predictor of pCR after NCT for EBC. Further evaluation of this predictive marker is clearly warrented. No significant financial relationships to disclose.